Time Travel in a Test Tube

In books and movies, time travel is typically fraught with negative consequences. Any attempt to change the past — say, stopping the JFK assassination, or taking your mom to the Enchantment Under the Sea dance — is bound to produce ripples of change that alter the future. But what if you could safely contain a trip back in time within the boundaries of a test tube? In a new paper published in Nature, a University of Chicago geneticist used a form of “molecular time travel” to observe a crucial event in the evolutionary history of life on Earth…and extinguish a favorite argument of intelligent design advocates.

The concept of “irreducible complexity” is a favorite talking point of the forces against evolution, both today and historically. As the argument goes, the complex structures found within modern organisms — from the eye to the microscopic protein machines that conduct business in cells — are far too complicated to be the result of the random genetic mutations and selective forces at the core of Darwin’s grand theory. The argument is so old that Darwin himself addressed it in On the Origin of Species, speculating on how an accumulation of small changes could lead from a simple photoreceptor to the wondrous eye shared by many organisms today.

The best way to demonstrate how the minute changes of evolution could produce great complexity is to capture that process in action. But to happen upon such a leap live would be a biological needle in an enormous haystack. A better strategy would be to pick a historic leap in complexity from the evolutionary past, and then go back and observe how it happened. Easy, right?

To accomplish this task, Joe Thornton, a new faculty member in the Departments of Human Genetics and Ecology & Evolution, developed the method of “molecular time travel.” Instead of a Delorean, Thornton’s method uses a computational analysis of the genes from modern-day species to resurrect the genes of ancestral species that lived hundreds of millions of years ago. For the new paper, Thornton and colleagues at the University of Oregon decided to “travel” back to look at a complex molecular machine found in various species of fungus.

“Our strategy was to use ‘molecular time travel’ to reconstruct and experimentally characterize all the proteins in this molecular machine just before and after it increased in complexity,” said Thornton, professor of human genetics and evolution & ecology at the University of Chicago, professor of biology at the University of Oregon, and an Early Career Scientist of the Howard Hughes Medical Institute. “By reconstructing the machine’s components as they existed in the deep past,” Thornton said, “we were able to establish exactly how each protein’s function changed over time and identify the specific genetic mutations that caused the machine to become more elaborate.”

Their target was a molecular machine called the V-ATPase proton pump, which helps maintain the proper acidity of compartments within cells. In modern Fungi, this pump contains a six-part ring made up of three separate proteins, but that wasn’t always the case. Some 800 million years ago, that same ring was made from only two proteins, meaning some kind of event occurred around then to increase the complexity of this machine.

Thornton’s group calculated the genetic sequence of the ring proteins from that ancient ancestor using the sequences of 139 modern Fungi family members, computationally tracing their common elements back up the Tree of Life to their ancient predecessor. The researchers could then reproduce the protein before the split (called Anc.3-11) and the two proteins that came after the split (Anc.3 and Anc.11), and see how they functioned in the proton pump’s ring.

Surprisingly, the “newer” proteins were less versatile than the ancestral Anc.3-11, which could substitute for either of its descendants when transplanted into modern Fungi. The result suggests that the pump’s increase in complexity resulted not from the evolution of a new, “better-designed” function, but from an initial loss of versatility.

“It’s counter-intuitive but simple: complexity increased because protein functions were lost, not gained,” Thornton said. “Just as in society, complexity increases when individuals and institutions forget how to be generalists and come to depend on specialists with increasingly narrow capacities.”

The scientists also looked under the hood at exactly what genetic changes were responsible for the ancient shift from two ring proteins to three, finding that no tricky moves were required. A duplication of the Anc.3-11 gene and two single nucleotide mutations — both common genetic events — were all it took to split one gene into two and produce the more complex modern ring.

“The mechanisms for this increase in complexity are incredibly simple, common occurrences,” Thornton said. “Gene duplications happen frequently in cells, and it’s easy for errors in copying to DNA to knock out a protein’s ability to interact with certain partners. It’s not as if evolution needed to happen upon some special combination of 100 mutations that created some complicated new function.”

That’s a direct hit upon the claim of intelligent design that extraordinary events were necessary to create the extraordinary molecular machines that make life possible. Thornton, no stranger to arguments with ID proponents, says that his simple experiment provides proof that small changes can lead to big biological effects, and expects that similar minute shifts with great consequences could be found driving the evolution of other seemingly irreducible elements.

“These really aren’t like precision-engineered machines at all,” he added. “They’re groups of molecules that happen to stick to each other, cobbled together during evolution by tinkering, degradation, and good luck, and preserved because they helped our ancestors to survive.”